Background and purpose
The chemokine monocyte chemoattractant protein‐1 (MCP‐1) is involved in the pathogenesis of Alzheimer’s disease (AD). This study aimed to investigate whether urinary MCP‐1 can ...distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects.
Methods
A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age‐ and sex‐matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP‐1 levels were determined using enzyme‐linked immunosorbent assays. The correlations between urinary MCP‐1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis.
Results
In the cohort of CN subjects of different ages, urinary MCP‐1 levels increased with ageing and were correlated with age. The urinary MCP‐1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age‐ and sex‐matched CN controls, urinary MCP‐1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP‐1 levels between the AD group and the aMCI group. The urinary MCP‐1 levels were correlated with the Mini‐Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects.
Conclusions
Urinary MCP‐1 is a potential biomarker for the diagnosis of AD and aMCI.
Stability and safety of rock structures are easily influenced by the dynamic disturbance, especially when weak joint planes exist. In order to investigate the filling joint effect on the dynamic ...response of rock specimens, a series of impact dynamic tests were conducted by a modified split Hopkinson pressure bar (SHPB) system. A sandwich type of sandstone specimens filling with different thicknesses layer of cemented mortar (filling joint) were tested in the study. The results show that the transmission coefficient, dynamic strength and energy absorption all decrease with increasing joint thickness. However, the reflection coefficient, peak strain and joint closure show an opposite variation trend. In addition, the deformation of the cemented mortar joint is the main reason to cause the deformation and final failure of jointed rock specimens. Tensile cracks dominate the fracturing behavior during the dynamic loading, but they have a slight influence on the final failure mode which transforms from localized slabbing to axial splitting failure with the filling joint becoming thicker.
Verticillium dahliae is a broad host-range pathogen that causes vascular wilts in plants. Interactions between three hosts and specific V. dahliae genotypes result in severe defoliation. The ...underlying mechanisms of defoliation are unresolved.
Genome resequencing, gene deletion and complementation, gene expression analysis, sequence divergence, defoliating phenotype identification, virulence analysis, and quantification of V. dahliae secondary metabolites were performed.
Population genomics previously revealed that G-LSR2 was horizontally transferred from the fungus Fusarium oxysporum f. sp. vasinfectum to V. dahliae and is exclusively found in the genomes of defoliating (D) strains. Deletion of seven genes within G-LSR2, designated as VdDf genes, produced the nondefoliation phenotype on cotton, olive, and okra but complementation of two genes restored the defoliation phenotype. Genes VdDf5 and VdDf6 associated with defoliation shared homology with polyketide synthases involved in secondary metabolism, whereas VdDf7 shared homology with proteins involved in the biosynthesis of N-lauroylethanolamine (N-acylethanolamine (NAE) 12:0), a compound that induces defoliation. NAE overbiosynthesis by D strains also appears to disrupt NAE metabolism in cotton by inducing overexpression of fatty acid amide hydrolase.
The VdDfs modulate the synthesis and overproduction of secondary metabolites, such as NAE 12:0, that cause defoliation either by altering abscisic acid sensitivity, hormone disruption, or sensitivity to the pathogen.
Low-dose computed tomography (LDCT) Non-Small Cell Lung (NSCLC) screening is associated with high false-positive rates, leading to unnecessary expensive and invasive follow ups. There is a need for ...minimally invasive approaches to improve the accuracy of NSCLC diagnosis. In addition, NSCLC patients harboring sensitizing mutations in epidermal growth factor receptor EGFR (T790M, L578R) are treated with Osimertinib, a potent tyrosine kinase inhibitor (TKI). However, nearly all patients develop TKI resistance. The underlying mechanisms are not fully understood. Plasma extracellular vesicle (EV) and circulating microRNA (miRNA) have been proposed as biomarkers for cancer screening and to inform treatment decisions. However, the identification of highly sensitive and broadly predictive core miRNA signatures remains a challenge. Also, how these systemic and diverse miRNAs impact cancer drug response is not well understood. Using an integrative approach, we examined plasma EV and circulating miRNA isolated from NSCLC patients versus screening controls with a similar risk profile. We found that combining EV (Hsa-miR-184, Let-7b-5p) and circulating (Hsa-miR-22-3p) miRNAs abundance robustly discriminates between NSCLC patients and high-risk cancer-free controls. Further, we found that Hsa-miR-22-3p, Hsa-miR-184, and Let-7b-5p functionally converge on WNT/βcatenin and mTOR/AKT signaling axes, known cancer therapy resistance signals. Targeting Hsa-miR-22-3p and Hsa-miR-184 desensitized EGFR-mutated (T790M, L578R) NSCLC cells to Osimertinib. These findings suggest that the expression levels of circulating hsa-miR-22-3p combined with EV hsa-miR-184 and Let-7b-5p levels potentially define a core biomarker signature for improving the accuracy of NSCLC diagnosis. Importantly, these biomarkers have the potential to enable prospective identification of patients who are at risk of responding poorly to Osimertinib alone but likely to benefit from Osimertinib/AKT blockade combination treatments.
Mesenchymal cells expressing platelet-derived growth factor receptor beta (PDGFRβ) are known to be important in fibrosis of organs such as the liver and kidney. Here we show that PDGFRβ
cells ...contribute to skeletal muscle and cardiac fibrosis via a mechanism that depends on αv integrins. Mice in which αv integrin is depleted in PDGFRβ
cells are protected from cardiotoxin and laceration-induced skeletal muscle fibrosis and angiotensin II-induced cardiac fibrosis. In addition, a small-molecule inhibitor of αv integrins attenuates fibrosis, even when pre-established, in both skeletal and cardiac muscle, and improves skeletal muscle function. αv integrin blockade also reduces TGFβ activation in primary human skeletal muscle and cardiac PDGFRβ
cells, suggesting that αv integrin inhibitors may be effective for the treatment and prevention of a broad range of muscle fibroses.
The plastic deformation behavior of Ti–22.4Nb–0.73Ta–2Zr–1.34O alloy was investigated by compression testing at room temperature. The multi-peak stress oscillations of the true stress–strain curve, ...characterized by a stress plateau, initial strain-hardening, followed by strain-softening and a second strain-hardening stages, is observed in a titanium alloy for the first time. The experimental results show that the above four-stage plastic deformation behavior is caused by a change in the dominant deformation mechanisms. At the stress plateau stage, the alloy deforms via multiple plastic deformation mechanisms. The initial strain hardening is caused mainly by tangling of dislocations. Subsequent strain softening is due to the formation of kink bands. The second strain hardening corresponds to the formation of shear bands. The above results suggest that the dominant deformation mechanisms of Ti–Nb–Ta–Zr–O alloys are related not only to the stability of the β phase, but also to the extent of plastic deformation.
RNA m
A modification is the most widely distributed RNA methylation and is closely related to various pathophysiological processes. Although the benefit of regular exercise on the heart has been well ...recognized, the role of RNA m
A in exercise training and exercise-induced physiological cardiac hypertrophy remains largely unknown. Here, we show that endurance exercise training leads to reduced cardiac mRNA m
A levels. METTL14 is downregulated by exercise, both at the level of RNA m
A and at the protein level. In vivo, wild-type METTL14 overexpression, but not MTase inactive mutant METTL14, blocks exercise-induced physiological cardiac hypertrophy. Cardiac-specific METTL14 knockdown attenuates acute ischemia-reperfusion injury as well as cardiac dysfunction in ischemia-reperfusion remodeling. Mechanistically, silencing METTL14 suppresses Phlpp2 mRNA m
A modifications and activates Akt-S473, in turn regulating cardiomyocyte growth and apoptosis. Our data indicates that METTL14 plays an important role in maintaining cardiac homeostasis. METTL14 downregulation represents a promising therapeutic strategy to attenuate cardiac remodeling.
High-Speed and Low-Energy Nitride Memristors Choi, Byung Joon; Torrezan, Antonio C.; Strachan, John Paul ...
Advanced functional materials,
August 2, 2016, Volume:
26, Issue:
29
Journal Article
Peer reviewed
Open access
High‐performance memristors based on AlN films have been demonstrated, which exhibit ultrafast ON/OFF switching times (≈85 ps for microdevices with waveguide) and relatively low switching current ...(≈15 μA for 50 nm devices). Physical characterizations are carried out to understand the device switching mechanism, and rationalize speed and energy performance. The formation of an Al‐rich conduction channel through the AlN layer is revealed. The motion of positively charged nitrogen vacancies is likely responsible for the observed switching.
Ultrafast switching of an AlN memristor: ON switching is acheived using an 85 ps positive voltage pulse, and OFF switching using an 85 ps negative voltage pulse on the Al electrode of a Pt/AlN/Al memristor stack. A relatively low switching current (≈15 μA for 50 nm devices) has also been demonstrated in these memristors based on AlN films. The formation of an Al‐rich conduction channel through the AlN layer is revealed.
•Pore structure and pore types of coal samples were analyzed by SEM images.•FIB-SEM and X-ray μ-CT were combined to characterize the 3-D pore-fracture networks of coals.•Multi-scale porosity, ...interconnectivity and pore size distribution were calculated by Avizo PNM.•The influence of 3-D pore-fracture networks on CBM storage and transport were discussed.
To study the three-dimensional (3-D) pore-fracture networks of bituminous (BC) and anthracite (AC) coals, a combination of focused-ion beam-scanning electron microscopy (FIB-SEM) tomography and X-ray computed micro-tomography (X-ray μ-CT) was used to characterize 3-D pore-fracture characteristics at different scales. First, as observed in the SEM images, organic-matter (OM) pores, shrinkage-induced pores and dissolution pores are developed in BC samples with pore sizes ranging from ∼25nm to 600nm, and are independently distributed within OM and partial pores filled with minerals. In contrast, a large number of gas pores are widely developed in the AC sample with a cluster distribution in OM, and the pore widths range from ∼10nm to 2μm. Second, we reconstructed the 3-D pore-fracture networks of the BC and AC samples, and quantitatively characterized the porosity, 3-D pore-throat characteristics and its connectivity using the Pore Network Model (PNM) in Avizo. The results indicate that the pores in the BC sample are poorly connected and isolated from each other, whereas the pores in the AC sample are well connected by the throats. There is a logarithmic correlation between the cumulative throat volume and throat size, indicating that the smaller throats make the main contribution to the throat volume. Moreover, the normalized pore size distribution obtained from FIB-SEM and X-ray μ-CT analysis shows that both BC and AC samples exhibit a three-peak structure, but the nano-scale pores are more developed in the AC sample and its 3-D pore morphologies are more complex than those of the BC sample. Furthermore, the macro-pores and micro-fractures in the two coal samples show complex spatial distribution, interconnectivity and tortuosity. The total resolved porosity is 1.108% for BC samples consisting of 0.279% of FIB-SEM and 0.829% of X-ray μ-CT, and 6.082% for AC sample composed of 4.194% of FIB-SEM and 1.888% of X-ray μ-CT, including the connected and non-connected porosity. These results show that the pore-fracture networks of the AC sample are more conducive to CBM storage and flow ability than those of the BC sample. Therefore, this finding provides an accurate method of evaluating the physical properties of coal reservoirs and assists in understanding the mechanisms of CBM storage and transport.
Context. The space mission Kepler provides us with long and uninterrupted photometric time series of red giants. We are now able to probe the rotational behaviour in their deep interiors using the ...observations of mixed modes. Aims. We aim to measure the rotational splittings in red giants and to derive scaling relations for rotation related to seismic and fundamental stellar parameters. Methods. We have developed a dedicated method for automated measurements of the rotational splittings in a large number of red giants. Ensemble asteroseismology, namely the examination of a large number of red giants at different stages of their evolution, allows us to derive global information on stellar evolution. Results. We have measured rotational splittings in a sample of about 300 red giants. We have also shown that these splittings are dominated by the core rotation. Under the assumption that a linear analysis can provide the rotational splitting, we observe a small increase of the core rotation of stars ascending the red giant branch. Alternatively, an important slow down is observed for red-clump stars compared to the red giant branch. We also show that, at fixed stellar radius, the specific angular momentum increases with increasing stellar mass. Conclusions. Ensemble asteroseismology indicates what has been indirectly suspected for a while: our interpretation of the observed rotational splittings leads to the conclusion that the mean core rotation significantly slows down during the red giant phase. The slow-down occurs in the last stages of the red giant branch. This spinning down explains, for instance, the long rotation periods measured in white dwarfs.
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